rs758185

Variant names:

• chr17-12731898-C-G
• rs758185
• NM_001146312.3:c.416-4263C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001146312.3(MYOCD):​c.416-4263C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.562 in 152,058 control chromosomes in the GnomAD database, including 24,254 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.56 (24254 hom., cov: 32)
• Consequence: MYOCD NM_001146312.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.726
• Publications: 3 publications found

Genes affected

MYOCD (HGNC:16067): (myocardin) This gene encodes a nuclear protein, which is expressed in heart, aorta, and in smooth muscle cell-containing tissues. It functions as a transcriptional co-activator of serum response factor (SRF) and modulates expression of cardiac and smooth muscle-specific SRF-target genes, and thus may play a crucial role in cardiogenesis and differentiation of the smooth muscle cell lineage. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Sep 2009]

MYOCD Gene-Disease associations (from GenCC):

• megabladder, congenital

  Inheritance: AD, Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.674 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYOCD	NM_001146312.3	c.416-4263C>G		intron_variant	Intron 5 of 13	ENST00000425538.6	NP_001139784.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYOCD	ENST00000425538.6	c.416-4263C>G		intron_variant	Intron 5 of 13	1	NM_001146312.3	ENSP00000401678.1
MYOCD	ENST00000343344.8	c.416-4263C>G		intron_variant	Intron 5 of 12	1		ENSP00000341835.4
MYOCD	ENST00000395988.1	n.336-4263C>G		intron_variant	Intron 2 of 8	2

Frequencies

GnomAD3 genomes AF: 0.562 AC: 85344 AN: 151940 Hom.: 24201 Cov.: 32

Gnomad AFR AF: 0.636

Gnomad AMI AF: 0.507

Gnomad AMR AF: 0.570

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.693

Gnomad SAS AF: 0.546

Gnomad FIN AF: 0.585

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.509

Gnomad OTH AF: 0.529

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.562 AC: 85461 AN: 152058 Hom.: 24254 Cov.: 32 AF XY: 0.565 AC XY: 42002 AN XY: 74310

African (AFR) AF: 0.637 AC: 26419 AN: 41464

American (AMR) AF: 0.570 AC: 8722 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.465 AC: 1612 AN: 3470

East Asian (EAS) AF: 0.693 AC: 3564 AN: 5146

South Asian (SAS) AF: 0.547 AC: 2634 AN: 4818

European-Finnish (FIN) AF: 0.585 AC: 6184 AN: 10564

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.509 AC: 34627 AN: 67990

Other (OTH) AF: 0.529 AC: 1116 AN: 2110

Alfa AF: 0.547 Hom.: 2794

Bravo AF: 0.567

Asia WGS AF: 0.600 AC: 2089 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.25
DANN	Benign	0.35
PhyloP100		-0.73
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs758185; hg19: chr17-12635215;